Glioblastoma multiforme (GBM) are highly malignant and invasive tumors. It not only can prevent total surgical resection, but also render these neoplasms refractory to cheJR-AB2-011 is a selective mTORC2 inhibitor with an IC50 value of 0.36 μM. JR-AB2-011 inhibits mTORC2 activity by blocking Rictor-mTOR association (Ki: 0.19 μM). JR-AB2-011 has anti-glioblastoma multiforme (GBM) propertiesmotherapeutic interventions. Thus, exploiting novel therapeutic options is necessary while circumventing resistance mechanisms. The mechanistic target of rapamycin (mTOR) kinase is the major mediator of phosphatidylinositol 3-kinase (PI-3K) signaling. Meanwhile, It is also an important target for molecular therapeutics in GBM.

mTOR-mLST8-Raptor complex (mTORC1) and mTOR-mLST8-mSIN1-Rictor complex (mTORC2) have a common element mTOR. But, They perform several different functions. Recent data indicate that mTORC2 activity is essential for characteristics of these tumors, including transformation and invasion. JR-AB2-011 is an inhibitor of mTORC2 with an IC₅₀ value of 0.36 μM, which specifically blocks the interaction of the regulatory subunit Rictor with mTOR. However, mTORC1 signaling is unaffected.

In vitro, JR-AB2-011 at dosing regimens markedly enhances apoptosis according to cellular assays. Furthermore, JR-AB2-011 displays the least toxicity to normal neurons with no significant cytotoxic effects for concentrations up to 10 mM compared to JR-AB2-000 analogs.

On the other hand, Compared to mice receiving vehicle alone, JR-AB2-011 at either dosing regimen displays marked inhibition of tumor growth rate. It is consistent with the effects on xenograft growth, Mice at either JR-AB2-011 dosing regimen significantly promotes survival relative to vehicle treated mice. Notably, mice tolerate both of these dosing regimens without obvious short or long-term toxicity or weight loss.

In summary, mTORC2 is a viable therapeutic target in GBM. JR-AB2-011 inhibitor blocks mTORC2 signaling in these tumors, which shows significant anti-tumor properties.